The primary long-term objective of this proposed project is the elucidation of the mechanisms involved in the physiological regulation of single nephron hemodynamics and the phenomenon of renal autoregulation. This objective is closely associated with the additional goals related to the quantitative characterization of the control of glomerular filtration rate and the determination of the influence of changes in glomerular function on the overall control of sodium and fluid excretion. Recent developments have highlighted the potential significance of the distal tubular feedback mechanism in the intrinsic regulation of renal vascular resistance and glomerular filtration rate. The work projected for this project period will delve further into the physiology of this feedback mechanism and is oriented towards: a) clarification of the specific intraluminal compositional component most closely associated with mediation of feedback signals from the macula densa cells to the vascular elements, b) quantification of the relationship between this intraluminal component and feedback mediated changes in glomerular hemodynamics, c) identification of the cellular events responsible for mediation of feedback signals and the potential contribution of certain intrarenal hormone systems to this process, d) evaluation of factors that alter the sensitivity of the feedback mechanism or modulate receptor responsiveness, and e) determination of specific feedback mediated alterations in the deteminants of glomerular filtration rate. Related experiments will focus on the effects of selected vasodilator and vasoconstrictor agents on the segmental vascular resistance and on the determinants of glomerular filtration rate in the dog. Most studies will involve the application of micropuncture techniques in order to assess directly the changes in single nephron function. Distal nephron microperfusion techniques and coincident distal tubule fluid collections will be utilized to evaluate the role of various substances proposed as feedback mediators.